There are various options for the treatment of heart failure, including pharmacological treatment, coronary revascularization and mitral valve surgery, and devices such as pacemakers, including cardiac resynchronization therapy, or ventricular assist devices. Therapies aimed at primarily slowing the heart rate down have all been used effectively to stabilize patients in New York Heart Association (NYHA) Class II and III heart failure, decreasing morbidity and mortality and prolonging the progression to more severe heart failure. These include vagus nerve electrical stimulation and pharmacologic agents such as Beta sympathetic adrenergic blockers or ivabradine (a selective inhibitor of the If current in the sinoatrial node without inotropic effects).
One pharmacological treatment option now reserved primarily for severe heart failure is the use of inotropic agents, such as dopamine and dobutamine. When the diseased ventricle has sufficient reserve capacity, this therapy can be very effective for increasing cardiac output. However, inotropic agents have both chronotropic (increase in heart rate) and inotropic (increase in ventricular contraction) effects. The chronotropic effect may be undesirable in patients in end stage heart failure because the rise in heart rate increases myocardial oxygen consumption. These patients have very limited reserve capacity to increase cardiac output at the expense of increasing myocardial oxygen demands. As a result, although these inotropic agents are used to increase myocardial contractility and improve hemodynamics in cases of acute and severe heart failure, clinical trials have consistently demonstrated an association between the use of inotropes and increased myocardial ischemia, arrhythmias and an increased risk of mortality. As such, there is a need for additional therapeutic regimes for the treatment of end stage heart failure that improves cardiac output without causing these undesirable effects on heart rate and myocardial oxygen consumption.